The thermoregulation of body temperature of mammals is of great importance to the medical profession. Certain types of operations, particularly heart operations, are desirably performed with lowered body temperature. Certain physiological disorders result in malfunctioning of the thermoregulative function of the body resulting in increased and uncontrollable body temperatures. It would be desirable to provide a pharmaceutically effective composition which can be used to reduce the body temperature either from an undesirably high temperature or in preparation for medical treatment.
The tridecapeptide, neurotensin, has been isolated and characterized from bovine hypothalamus. Neurotensin has the structure: EQU p-Glu-Leu-Tyr-Glu-Asn-Lys-Pro-Arg-Arg-Pro-Tyr-Ile-Leu-OH
Neurotensin has been reported to have a body temperature-lowering effect; G. Bissette et al, Nature 262: 607 (1976). In the studies reported in the G. Bissette et al article, neurotensin given intracisternally but not intravenously, produced a lowering of basal body temperature of mice at room temperature or exposed to cold (4.degree. C.). However, the body temperature lowering effect of neurotensin is not sufficient for practical pharmaceutical and operative use.
U.S. Pat. No. 4,207,311, issued June 10, 1980 to Marvin R. Brown, et al. discloses the structure of bombesin and other related peptides which have been isolated from the skin of several anuran species. Amphibian bombesin has the formula: EQU pGlu-Gln-Arg-Leu-Gly-Asn-Gln-Trp-Ala-Val-Gly-His-Leu-Met-NH.sub.2
The patent discloses that the administration of bombesin to mammals, including humans, can be used for reducing the body temperature of the mammal as well as for inducing analgesia. The patent also discloses several analogs of bombesin which exhibit certain analgesic and thermoregulative effects in mammals including the octapeptide D-pGlu-Trp-Ala-Val-D-Ala-His-Leu-Met-NH.sub.2. Although this octapeptide is more potent than neurotensin, it is less potent than bombesin, and more potent analogs having these properties would be of great value.